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发表于 2021-1-25 15:59:06
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The specificity of host-pathogen interactions with emphasis on the specific inhibitor proteins synthesized in the invasion-defense process.
1.Pathogen S. aureus VS. Human
Staphylococcal aureus complement inhibitor (SCIN) of protein was discovered [1]. SCIN infects a broad range of animal species, including horses, humans, pigs, which is evolved into strong adaptiveness through genome modification (such as by gene communications with external genetic segments aiming to host-invasion interactions). For the human S. aureus, a specific variant stream was found to block human complement system; for the horse S. aureus, the specific equine variant of SCIN was indicated to inhibit the horse complement system.
Accordingly, A specific Human monoclonal antibodies (humAbs), named as 6D4, was abstracted from B-cells screened randomly, which specifically binds the SCIN and C3 convertases as inhibitors against S. aureus[2].
In this article, it is further proposed that compared with S. aureus that evolves across host animal species with closer genetic distances, COVID-19 virus originates from the wild species with longer genetic distance to human, which is evolved into adaptation on human host by acquisition of human gene segments for self-modification of virus genome. This is one of the key factor to explain why COVID-19 is more epidemic than before.
2.The inhibition protein over a broader range of biological phyla.
The specificity of host–pathogen interactions in pathogenesis against melanin synthesized by the host cells of invertebrates, which is activated by prophenoloxidase pathway of metabolic process, is discussed [3]. Further more, there are totally six families of serine proteinase inhibitors, including Kazal, Kunitz, α-macroglobulin, Serpin and two recently reported families of low molecule weight [4], which functions in arthropod hemolymph immunology system to defense against a broad ranges of pathogens or parasites infections. Several families of protein protease inhibitors are classified into two classes according to the different functions played in the binding process: the active site inhibition protease families and a specific family of α2-macroglobulins[5]. The first class inhibitors directly bind and inactivate the active site of the pathogenic protease, whereas the second protein α2-macroglobulins bind protease of invasive pathogens by a unique molecular trap mechanism in which α2-macroglobulins converts the bound protease into a receptor-mediated endocytic system, subsequently degradation occurs in secondary lysosomes. The α2-macroglobulins are reported in a wide range of biological phyla, which is consequently considered as the expression of conserved chromosome arm in the 0.6 billion evolutionary process.
In this article, it is further suggested that the functional group triggering the catalytic reaction of the same isozyme family is expressed by the conserved genomes in the evolutionary process, so the above protein protease families summarized also becomes the chemical species for isozyme development, which can be commonly used in other biological species.
To be continued....
References
[1]De Jong NWM, Vrieling M, Garcia BL, Koop G, Brettmann M, Aerts PC, Ruyken M, van Strijp JAG, Holmes M, Harrison EM, Geisbrecht BV, Rooijakkers SHM. Identification of a staphylococcal complement inhibitor with broad host specificity in equid Staphylococcus aureus strains. J Biol Chem. 2018 Mar 23;293(12):4468-4477. doi: 10.1074/jbc.RA117.000599. Epub 2018 Feb 5. PMID: 29414776; PMCID: PMC5868266.
[2]Hoekstra H, Romero Pastrana F, Bonarius HPJ, van Kessel KPM, Elsinga GS, Kooi N, Groen H, van Dijl JM, Buist G. A human monoclonal antibody that specifically binds and inhibits the staphylococcal complement inhibitor protein SCIN. Virulence. 2018 Jan 1;9(1):70-82. doi: 10.1080/21505594.2017.1294297. Epub 2017 May 8. PMID: 28277903; PMCID: PMC5955450.
[3].Lage Cerenius, Bok Luel Lee, Kenneth Söderhäll, The proPO-system: pros and cons for its role in invertebrate immunity,Trends in Immunology, Volume 29, Issue 6,2008,Pages 263-271,ISSN 1471-4906.
[4].Michael R. Kanost, Serine proteinase inhibitors in arthropod immunity,
Developmental & Comparative Immunology, Volume 23, Issues 4–5,1999,Pages 291-301,ISSN 0145-305X.
[5].Peter B. Armstrong, Proteases and protease inhibitors: a balance of activities in host–pathogen interaction, Immunobiology, Volume 211, Issue 4,
2006, Pages 263-281, ISSN 0171-2985.
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